CAJ | 학술논문

目的研究心肺复苏后大鼠心肌细胞缺氧诱导因子-1α(hypoxia-inducible factor-1α,HIF-1α)的变化及外源性硫化氢(hydrogen sulfide,H2S)的干预作用.方法实验在华中科技大学同济医学院附属同济医院动物实验室进行,雄性SD大鼠45只,采用窒息法建立大鼠心搏骤停模型,随机(随机数字法)分为3组,每组15只:(1)对照组,仅行麻醉、气管插管及动静脉插管操作;(2)CPR组,进行模型制备及复苏;(3)CPR+硫氢化钠(NaHS)组,以NaHS作为H2S供体,在CPR开始前1 min经股静脉给予50μg /kg NaHS,其余操作同CPR组.观察各组血流动力学参数,留取6 h心肌组织,采用RT-PCR法检测HIF-1α mRNA表达,采用MPO测定试剂盒测定各组心肌组织MPO含量,三组动物于24 h处死取心肌组织行病理学检查.采用单因素方差分析,组阳比较采用t检验.结果 CPR组和CPR+NaHS组的血流动力学指标差异无统计学意义(P＞0.05).与对照组相比,CPR组和CPR+NaHS组HIF-1α基因表达均上升,CPR+NaHS组上升更为显著(P＜0.05),与CPR组比较,CPR+NaHS组HIF-1α基因表达升高(P＜0.06);与对照组相比,CPR组和CPR+NaHS组心肌MPO活性出现不同程度升高(P＜0.05),与CPR组比较,CPR+NaHS组心肌MPO活性下降(P＜0.05);通过对心肌苏木精-伊红(HE)染色切片观察显示,CPR组和CPR+NaHS组出现不同程度的病理损伤,GPR+NaHS组的病理损伤轻于CPR组.结论 HIF-1α mRNA在心肺复苏后大鼠心肌细胞的表达增强,硫化氢可能通过上调HIF-1α的表达,对心肺复苏后心肌起保护作用.
목적 연구심폐복소후대서심기세포결양유도인자-1α(hypoxia-inducible factor-1α,HIF-1α)적변화급외원성류화경(hydrogen sulfide,H2S)적간예작용.방법 실험재화중과기대학동제의학원부속동제의원동물실험실진행,웅성SD대서45지,채용질식법건립대서심박취정모형,수궤(수궤수자법)분위3조,매조15지:(1)대조조,부행마취、기관삽관급동정맥삽관조작;(2)CPR조,진행모형제비급복소;(3)CPR+류경화납(NaHS)조,이NaHS작위H2S공체,재CPR개시전1 min경고정맥급여50μg /kg NaHS,기여조작동CPR조.관찰각조혈류동역학삼수,류취6 h심기조직,채용RT-PCR법검측HIF-1α mRNA표체,채용MPO측정시제합측정각조심기조직MPO함량,삼조동물우24 h처사취심기조직행병이학검사.채용단인소방차분석,조양비교채용t검험.결과 CPR조화CPR+NaHS조적혈류동역학지표차이무통계학의의(P＞0.05).여대조조상비,CPR조화CPR+NaHS조HIF-1α기인표체균상승,CPR+NaHS조상승경위현저(P＜0.05),여CPR조비교,CPR+NaHS조HIF-1α기인표체승고(P＜0.06);여대조조상비,CPR조화CPR+NaHS조심기MPO활성출현불동정도승고(P＜0.05),여CPR조비교,CPR+NaHS조심기MPO활성하강(P＜0.05);통과대심기소목정-이홍(HE)염색절편관찰현시,CPR조화CPR+NaHS조출현불동정도적병리손상,GPR+NaHS조적병리손상경우CPR조.결론 HIF-1α mRNA재심폐복소후대서심기세포적표체증강,류화경가능통과상조HIF-1α적표체,대심폐복소후심기기보호작용.
Objective To investigate the changes of the expression of HIF-1α (hypoxia induciblefactor-1a) mRNA in myocardium of rats after cardiopulmonary resuscitation (CPR) and the intervention effects of exogenous hydrogen sulfide on it. Method Forty five male SD rats were randomly divided into three groups: control group ( n = 15 ), cardiopulmonary resuscitation group ( CPR group, n = 15 ) and NaHS + CPR group (n = 15 ) . Rats of control group were anesthetized and intubated without asphyxia and cardiac arrest. The rats of CPR group and NaHS + CPR group were operated to induce cardiac arrest by asphyxiation. In the rats of NaHS + CPR group, NaHS in dose of 50 ug/kg was administrated via the femoral venous line 1 minute before CPR. Hemodynamic was monitored continuously. The expression of HIF - lα mRNA in myocardium of rats in each group was determined by using RT-PCR and the activity of myeloperoxidase (MPO) in the myocardium of rats in each group was assayed by using a patent reagent box 6 h after CPR. The histopathological changes of myocardium were also observed. The t- test was used for statistical analysis. Results There was no statistically significant difference in hemodynamic changes between CPR group and CPR + NaHS group ( P ＞ 0. 05 ) . When compared with the control group, the activity of MPO and the expression of HIF-1α mRNA in CPR group and CPR + NaHS group were both increased, and those increased in CPR + NaHS group was more significant (P ＜ 0. 05) . When compared with CPR group, the expression of HIF-1α mRNA in CPR + NaHS group was higher, however, the activity of MPO in CPR + NaHS group was lower ( P ＜ 0. 05) . There were various histopathological changes of myocardium of rats found in CPR group and CPR + NaHS group, and the damage of myocardium of rats in CPR group was more obvious than that in CPR + NaHS group. Conclusions The expression of HIF-1α mRNA in myocardium of rats was increased after CPR. Exogenous hydrogen sulfide can protect myocardium cells from resuscitation-perfusion injury, and the protection is associated with increase in expression of HIF 1 αmRNA.